Validation of Controlled Freezing and Thawing Rates: A 16-L–Bag Study

It is well understood that freeze– thaw processes affect the product quality of biopharmaceuticals (1–3). It has been reported that there is no consistent method of controlled freezing and thawing rates for biological formulations (4). Traditionally, ultralow temperature storage chambers that were not designed for freezing have been used to provide an energy state for the environment surrounding the product with very little excess capacity to change the state of the product.

This study details a consistent method for controlled-rate freezing and thawing. It also includes the effect of load and container position on freeze rates. The freeze–thaw controlled-rate chamber used in this study was a model 4002 manufactured by Farrar Scientific. It permits rapid, uniform bulk freezing and/or thawing of products with temperature ranges from 40 °C to –80 °C. It has a minimum of 1.7 kW of net cooling and heating capacity over the entire temperature range and offers the flexibility of programmable profiles.